tbuckley/cabot-search huggingface dataset:
P08.07.B TRANSITION CLINIC IN NEURO-ONCOLOGY WHICH MODEL IS BETTER? THE PATIENT'S OPINION
Authors: A Azuelos, O Haisraely, N Atar, E Jan, A Taliansky
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND The period between adolescence and adulthood is important and complicated for all people. Is much more complicated for young adults (YA) that were diagnosed and treated for central nervous system (CNS) tumors in childhood and adolescence. They have to continue a lifelong multidisciplinary surveillance that is time and energy consuming. Patients that does not have any or significant neurological deficit desire to start a ”normal” to age life that includes independence from the parents and reduction of hours spent in the hospital. They try to undergo surveillance in community health services but that way is complicated and the surveillance is made irregularly or not at all. If they undergo surveillance in hospitals where it is regularly made, the patients lose school or work days and suffer from high anxiety level because of the “to be a patient again ” feeling . Attempts to create the optimal surveillance model for those patients were made, but the best model is still unknown. MATERIAL AND METHODS We questioned CNS tumor patients 20-40 years old that were transferred from a pediatric to an adult neuro-oncology service in Sheba MC. RESULTS The response from 38 patients was obtained: 11 patients with pilocytic astrocytomas, 11 other gliomas, 3 gangliogliomas, 2 germ cell tumors, 3 medulloblastomas, 3 NF1 patients with optic pathway gliomas, 4 with pineal region tumors, 1 with immature teratoma. 33% of patients are married and live with the spouse, 55% live with their parents, 4 % live by themselves. Of the respondents 18 % are students and 47% are permanently employed. Most of the patients prefer to undergo surveillances in community health services and visit hospitals as rare as possible. All patients expressed an understanding of the importance of a lifelong surveillance as recommend by the treating neuro-oncologist. The patients strongly expressed the need to have a dedicated case coordinator that can help organize the test’s flexible timetable and an effective communication between the teams CONCLUSION According to our patient’s opinion, the preferable model of surveillance for high functioning YA CNS tumor patients is the cooperation of the hospital’s neuro-oncology unit and the community health service. The first is responsible for planning the surveillance and taking the appropriate medical actions according to the RESULTS . The second is responsible for the realization of the program. The assignment of a case coordinator that connects between all of the teams is crucial.
P20.12.B DNA METHYLATION PROFILING OF ADULT SPINAL GLIAL TUMOURS; RESULTS FROM A LARGE SINGLE CENTRE STUDY
Authors: M T Clarke, R Pereira, A Mackay, Y Grabovska, R Cruickshank, M Dutt, P Mariathasan, A Kumar, A Casey, A Merve, Z Jaunmuktane, C Jones, S Brandner
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Glial tumours can occur in any central nervous system location, including the spinal cord. Although rare, spinal gliomas can represent a significant diagnostic challenge and are recognised as separate tumour types in the WHO classification. MATERIAL AND METHODS This study used DNA methylation profiling to characterise adult spinal glial tumours from a large neurosurgical centre, exploring relative frequencies, and the value of this technique in diagnostic workflows. A search in our laboratory information management system (2006-2021) identified 116 tumours, from patients aged 17.2-79.2 years. Diagnoses included ependymomas (all grades/subtypes) and other high- or low-grade gliomas (HGG/LGG). Extrinsic tumours (metastases, meningiomas, schwannomas) were excluded. DNA underwent methylation profiling (Illumina EPIC BeadArrays, n=116). iDat files were processed using the brain tumour classifier (MNP v12.5 R package), classifying cases against a reference cohort (n=2,800). Longitudinal (n=8) and poor QC cases (n=3) were excluded. RESULTS 83% (n=87) classified as an ependymoma (myxopapillary ependymoma (EPN_MPE, n=44), spinal ependymoma (n=43), spinal subependymoma (n=1)). We identified HGGs that were not diagnosed histologically (diffuse midline glioma, H3 K27-altered (n=2), high-grade astrocytoma with piloid features (n=1)) and 41% of cases (n=18/44) diagnosed histologically as an ependymoma, CNS WHO grade 2, classified as EPN_MPE. LGGs were less frequent (pilocytic astrocytoma (n=3), pleomorphic xanthoastrocytoma (n=1), rosette-forming glioneuronal tumour (n=1)). 9% (n=9) did not classify with existing methylation classes. Copy number analysis revealed subtype-specific changes, including prognostic alterations. CONCLUSION In conclusion, this single-centre study highlights the crucial role of DNA methylation profiling as part of diagnostic workflows for spinal glial tumours.
P11.12.B SEIZURES IN PATIENTS WITH BRAIN METASTASES FROM BREAST CANCER: RESULTS FROM A RETROSPECTIVE SINGLE-CENTRE STUDY
Authors: F Bruno, A Pellerino, M Borgognone, R Palmiero, L Bertero, E M Marchesani, D Garbossa, R Soffietti, R Rudà
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Seizures may be a symptom of brain metastases (BrMs) from breast cancer. Gross-total resection (GTR) is known to correlate with a better seizure control, while the impact of radiotherapy (RT) and chemotherapy (CT) still remains uncertain. In this study, we aimed to explore which clinical and molecular factors might affect seizure control in a cohort of patients with BrMs from breast cancer. Patients and METHODS We retrospectively included patients ≥18 with surgically resected BrMs from primary breast cancer treated in our Institution from 1991 to 2022. RESULTS We included 79 patients in the analysis. Thirty-three (41.7%) had a history of seizures. Seizures prevailed in patients &amp;lt; 50 vs ≥ 50 (59.0% vs 32.0%, p=0.021), and they were not associated with BrMs location, number, or morphology (cystic vs non-cystic; bleeding vs non-bleeding). Patients with low (score 0-1) vs high (score 2-3) STAT3 expression in the peritumoural reactive astrocytes (RAs) had a slightly higher incidence of seizures (50.0% vs 35.0%, p=0.337). Seizure incidence did not differ between HER2+, HR+/HER2- and TNBC patients. Seizures tended to be more common after non-GTR as compared with GTR (21.0% vs 11.0%, p=0.293). RT and CT did not affect seizure control. CONCLUSION Younger age was associated with a higher risk of seizures, whereas different molecular subgroups (HER2+, HR+/HER2-, TNBC) or STAT3 expression in the RAs were not. To our knowledge, this is the first real-life study investigating the correlation between seizures and clinical and molecular factors in patients with BrM from breast cancer.
P10.24.B SCREENING NON-ONCOLOGICAL DRUGS IN A PATIENT-DERIVED GLIOBLASTOMA MODEL IDENTIFIES PITAVASTATIN WITH POTENTIAL ANTITUMOR ACTIVITY
Authors: S Zekanovic, P Achaiber Sing, A Basuki, S L W Koolen, I Ntafoulis, C W J den Hollander, M P Chien, Y Li, D A M Mustafa, C M F Dirven, S Leenstra, M L M Lamfers
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Glioblastoma (GBM) is a malignancy which is in dire need of novel treatment options. Repurposing non-oncological drugs has become of great interest in GBM research. Non-oncological drugs have many advantages over their oncological counterparts including a well-established safety and toxicity profile, possibilities to perform dose escalation studies, and combinations with oncological drugs (e.g. temozolomide, TMZ). Making use of our patient-derived in vitro model which has been shown to recapitulate GBM in terms of genetic make-up and heterogeneity, we aim at identifying non-oncological drugs that exhibit potent antitumor activity. MATERIAL AND METHODS Drug screening was performed using an NIH clinical compound selection consisting of 446 non-oncological drugs on 2 patient-derived GBM cell lines. Viability 5 days post treatment was assessed using the ATP-based Cell Titer Glo assay. Validation studies were performed on a panel of 25 GBM cultures. Nanostring analysis using the Pan Cancer gene panel, flow cytometry, Western Blotting and immunofluorescence were employed to gain insight into drug mechanism of action. The zero-interaction potential method was used to quantify synergy with TMZ. Dose-modifying factors (DMF) were calculated to quantify synergy with irradiation. RESULTS Screening of 446 non-oncological drugs yielded a top 10 list of candidates which were evaluated on an additional cell panel. Based on safety and efficacy, pitavastatin, an HMG-CoA reductase inhibitor, was selected for further analysis. Compared to 8 other registered statins, pitavastatin revealed the most potent anti-tumor activity, with IC50 values in the low micromolar range. Pitavastatin efficacy was validated in a panel of 25 GBM cultures derived from various GBM subtypes in terms of primary/recurrence, MGMT and IDH status (IC50 ranging from 0.1 - 5.0 µM). GBM cultures derived from patients using statins for cholesterol management did not reveal resistance to pitavastatin. Combination treatment of pitavastatin with either TMZ or irradiation showed synergy with TMZ in 5/8 cultures and radiosensitizing effects in 3/5 cultures (DMF &amp;gt;2.0). Importantly, no antagonism was observed with TMZ or irradiation. Mechanistic studies demonstrated that pitavastatin treatment led to induction of autophagy, perturbations in GBM cell cycle and attenuation of GSC stemness through downregulation of SOX2 and CD133. CONCLUSION Drug screening on patient derived GBM cultures identified pitavastatin as a potent inhibitor of GBM cell viability and revealed its chemo- and radiosensitizing effects. Mechanistic studies suggest that its antitumor effects could be a consequence of autophagy induction, cell cycle arrest and loss of GBM cell stemness. Currently we are exploring strategies to ensure optimal intratumoral delivery in vivo.
P16.04.A THE PROGNOSTIC ROLE OF VENTRICULAR SIZE AND ITS DYNAMICS IN PATIENTS WITH LEPTOMENINGEAL METASTASIS FROM SOLID TUMORS
Authors: E Le Rhun, P Devos, K Seystahl, J Jongen, D Gramatzki, P Roth, M J van den Bent, L Regli, D Brandsma, M Weller
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Hydrocephalus is a common radiological sign in patients with leptomeningeal metastasis (LM) from solid tumors and can be assessed using the Evans index (EI) with high interrater agreement. Here we explored the prognostic value of ventricular size at diagnosis and during the disease course of LM. METHODS We assembled a cohort of 113 adult patients with a diagnosis of LM from solid extra-CNS tumors and explored the prognostic association of ventricular size assessed by the EI at diagnosis, of its modification between diagnosis and evaluation at first follow-up (&amp;gt;21 days after diagnosis), and at first progression. RESULTS Median age was 58.2 years (interquartile range (IQR) 46.1-65.7), 41 patients (36%) were male, the most frequent cancers were lung cancer (n=39, 35%), breast cancer (n=36, 32%) and melanoma (n=23, 20%). The median EI at baseline was 0.28 (IQR 0.26-0.31) and the EI value was 0.27 or more in 67 patients (59%) and 0.30 or more in 37 patients (33%). Among patients with MRI follow-up, the EI increased by 0.01 or more in 19 patients (40%), including 9 of 29 patients (30%) and 10 of 17 patients (59%), respectively, without and with LM progression at first follow-up. At LM progression, an increase of EI of 0.01 or more was noted in 18 of 34 patients (53%). The median overall survival was 2.9 months (IQR 1-7.2). Patients with a baseline EI of 0.26 or less had a longer survival than those with an EI of 0.27 or more (5.3 months, IQR 2.4-10.8, versus 1.3 months, IQR 0.6-4.1) (p=0.006). Median survival was 3.7 months (IQR 1.4-8.3) with an EI of 0.29 or less versus 1.8 months (IQR 0.8-4.1) with an EI of 0.30 or more (p=0.109). Among patients with follow-up scans available, median overall survival was 9.7 months (IQR 5.6-21.4) for patients with stable or decreased EI at first follow-up as opposed to 6.4 months (IQR 3.2-10.5) for those with an increase in the EI (p=0.292). CONCLUSION The EI at baseline is prognostic in LM. An increase of EI during the follow-up is associated with inferior LM-progression-free survival. An independent validation cohort with larger sample size and evaluation of confounding factors will help to better define the clinical utility of EI assessments in LM.
P10.30.B COMBINATION TREATMENT WITH ERIBULIN AND TTFIELDS INDUCES APOPTOSIS AND G2/M CELL CYCLE ARREST IN HUMAN GLIOBLASTOMA CELLS
Authors: H Goett, C Schön, P Beusker, E Uhl, M Stein
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND TTFields has emerged to a first line treatment in newly diagnosed glioblastoma (GBM) patients. Several preclinical studies showed that the alternating electric fields inhibit proliferation and survival of human glioblastoma cells by disruption of the spindle apparatus and impairment of mitotic segregation. Eribulin is an antimitotic drug, that is currently used in the third line treatment of breast cancer. As it is also able to inhibit the pro-mitotic function of TERT, which is mutated in 80% of human glioblastoma, the drug was also shown to have a radiosensitizing and antiproliferative effect on human glioblastoma and ovarian cancer cell lines. This study aims to evaluate the effect of the combination of Eribulin and TTFields on the survival and cell cycle of glioblastoma cells. MATERIAL AND METHODS U87, A172 and four patient derived glioblastoma cell lines were cultured and plated to 80% confluence. Cells were then treated with TTFields at a frequency of 200kHz for 24 hours and/or received the ED50 and 0.5-fold ED50 of Eribulin. Controls remained untreated respectively. After 24 hours cells were harvested and counted by automatic cell count. Survival and cell cycle status were evaluated by FACS analysis. RESULTS The rate of early apoptotic cells was 82.28% in the group treated with TTFields and Eribulin. With TTFields treatment only 50.99% and with Eribulin alone 14.38% of cells were in an early apoptotic state. Untreated control cells had an apoptosis rate of 4.25%. The combination of TTFields and Eribulin was significantly more effective than the single treatment modalities (p&amp;gt;0.05). Treatment with TTFields increased the rate of cells an G2/M status. This effect was even stronger in the group with combination treatment. CONCLUSION Combination treatment of the antimitotic drug Eribulin with TTFields is able to improve the inhibitory effect of the drugs on cell survival. Furthermore the combination therapy effects the cell cycle of glioblastoma cells inducing G2/M arrest. Future preclinical studies should focus on the antimitotic effect and the influence of the treatment on genome integrity for a more detailed insight into the mechanisms of action.
P07.15.B NEUROMUSCULAR HIGH-RESOLUTION ULTRASOUND IN PERIPHERAL NEUROTOXICITY OF SYSTEMICALLY TREATED CANCER PATIENTS
Authors: I Mäurer, J Hammersen, B Heiling, A Lawson McLean, C Risse, N A Leistner, S Schütze, U Schnetzke, M Schwab, I Hilgendorf, C Senft, S Hartinger
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Up to 40 % of cancer patients treated with neurotoxic cytostatic chemotherapies develop treatment-induced peripheral neuropathy. Furthermore, in patients treated with immune checkpoint inhibitors neuromuscular immune-related adverse events (irAEs) are the most common neurological complication. The differentiation between various types of peripheral neurotoxicity, neurological comorbidities and (para-)neoplastic conditions requires experienced clinical and neurophysiological diagnostics within an interdisciplinary team of experts. High-resolution ultrasound (HRUS) is a widely used diagnostic tool for peripheral neuropathies. As there are no generally approved biomarkers of treatment-related neurotoxicity so far, HRUS might extend the repertoire of diagnostic and neuromonitoring methods in patients with neuropathies induced by cytostatic agents, immunotherapy, and targeted therapy. MATERIAL AND METHODS We present the integration of HRUS into a standardized algorithm for suspected peripheral neurotoxicity by characterizing a case series from our neuro-oncological center. We show representative HRUS findings of seven cancer patients (diagnosed with breast cancer, cholangiocarcinoma, colorectal carcinoma, or multiple myeloma) treated with platinum derivates, immune checkpoint inhibitors, bortezomib, or lenalidomide. RESULTS We describe the potential of HRUS independently of a certain cancer treatment regimen and beyond that in patients with both neurological co-morbidities and concomitant neoplastic infiltration of the nervous system. In our retrospective cohort, HRUS revealed partly continuous and partly discontinuous nerve swelling as well as compression syndromes. Moreover, we detected enlargements of dorsal roots and vagus nerve in cancer patients with treatment-induced neuropathies for the first time. In addition, we identified significant discordance between clinical, electrophysiological and HRUS findings and discuss how peripheral neurotoxicity may be amenable to complementary HRUS assessment and neuromonitoring. CONCLUSION At our institution, neuromuscular ultrasound is an integral part of the interdisciplinary algorithm for peripheral neuropathies in systemically treated cancer patients. HRUS expands the neurological tool inventory for cancer patients and accelerates the differentiation of peripheral neurotoxicity, neurological comorbidities, and neoplastic affection of the nervous system in a non-invasive and cost-sparing manner. Our data may help to detect distinct patterns of nerve enlargement as new biomarkers of peripheral neurotoxicity. Thus, we employed our data to conduct a prospective, cross-sectional trial (PARTICIPATE), which has the potential to define the diagnostic relevance of HRUS for patients treated with agents affecting the PNS and its impact on cancer patient care.
P18.03.A HYPOFRACTIONATION WITH OPTIMIZED STEREOTACTIC RADIOSURGERY PLANNING FOR SKULL BASE PERIOPTIC MENINGIOMAS
Authors: Y Cho, K Yoon, D Lee, S Song, Y Kim, C Hong, J Kim
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Skull base perioptic meningiomas are challenging for stereotactic radiosurgery (SRS). The therapeutic window between tumor control and normal tissue complication is extremely narrow in these tumors, especially of large volume and/or in close proximity to the optic apparatus (OA). To minimize the risk of radiation toxicity, we optimized our SRS plans in terms of both steeper dose fall-off and dose-volume constraints for OA and delivered hypofractionation treatment. MATERIAL AND METHODS Thirty-one patients had been treated with hypofractionated SRS using the CyberKnife for perioptic meningiomas &amp;gt; 10 cm3 in volume (median 18.9 cm3). Tumor locations were cavernous sinus (n=7), petroclival (n=6), and tentorial edge (n=6). Optimization in SRS planning was carried in two aspects: 1) for steeper dose fall-off, multiple virtual shells outside the target were introduced and appropriate dose limits (formulated from our own Gamma Knife data) were applied; and 2) to minimize the risk of optic neuropathy, dose-volume constraints for OA (from AAPM TG101) were applied. SRS was delivered in five daily fractions with a median cumulative dose 27.8 Gy. RESULTS With a median follow-up of 33 months, tumor control was achieved in 28 of 31 patients (90.3%). Treatment response on MRI included partial response (volume decrease &amp;gt; 20%) in 17 patients, stable in 11, and progression (volume increase &amp;gt; 20%) in 3. Neurological symptoms improved in 10 patients, unchanged in 20, and worsened in 1. CONCLUSION Our current results show a promising role of hypofractionated SRS with optimization in steeper dose fall-off and dose-volume constraints for OA for large-sized skull base perioptic megningiomas in terms of both tumor control and neurological outcomes.
P18.09.A PROTON THERAPY FOR PATIENTS WITH MENINGIOMA - WHAT ABOUT FINANCIAL TOXICITY AND OCCUPATIONAL STATUS?
Authors: B Flechl, M Achtaewa, L Konrath, E Hug, P Fossati, M Pelak, P Georg, C Lütgendorf-Caucig
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Patients (pts) with meningioma are commonly treated with proton therapy (PT) in order to minimize integral dose to normal brain parenchyma. Considering the high local control probability, preservation of Quality of Life (QoL) is gaining increasing importance.Potential loss of employment, inability to work or need to reduce working hours may lead to financial worries negatively affecting QoL. We investigated the subjective QoL and disease burden in pts with meningioma treated with PT with regards to income, financial toxicity, inability to resume work before and after PT. MATERIAL AND METHODS Data from prospectively assessed questionnaires (EORTC QLQ-C30) including an item for subjective financial difficulties, scaled from 1-4 (1=“not at all” to 4=”very much”), was collected from pts treated with PT for meningioma. Observed time points were prior to start of treatment (t1) and incrementally thereafter (completion of treatment, at 3months (ms),6ms,12ms,24ms,36ms and 48ms;t2-t8). Employment status was collected and net household income was assessed and ranked into 5 groups ranging from &amp;lt;1300€ to &amp;gt;5000€. RESULTS: RESULTS 171pts (39m/131f) aged 20-88yrs (mean 55.1) with meningioma were included. At a mean observation time of 29.6ms, 991 data sets were collected. 37pts (35.9%) reported health-related inability to work before PT. Over follow up (FU), it decreased to 33.8% at 12ms, 27.3% at 24ms, 15.4% at 36ms, 13.6% at 48ms. 34pts (33%) were employed prior to their diagnosis (14part-time, 18full-time). While rates of full-time employment initially decreased, it steadily increased from 1yr FU (t3-t8: 28.7%-59.1%), rates of part-time remained stable (t3-t8:27.2%-27.3%), see figure 1. Subjective financial burden correlated significantly with occupational situation (Spearman;p&amp;lt;0.001) indicating a reduction in patient-reported financial difficulties after commencement of work / increase in working hours. There were no relevant changes in pts´ income (Friedman:p=0.610); however, pts with lower income prior to PT reported subsequently higher levels of financial difficulties (Spearman:p&amp;lt;0.001). Before PT, 69 pts (40%) reported various levels of financial difficulties. Although rates decreased initially at the end of PT (30.2%), they consistently decreased at all subsequent FUs. This reflects the lower burden of financial toxicity over time. CONCLUSION At a mean observation time of &amp;gt;2 years, this study prospectively analyzed the potential impact of proton therapy in patients treated for meningioma. Patients reported an overall increase in employment rate, significant improvement in their financial situation and preservation and gain in their quality of life over time.